The development of new processes by which the efficiency of pharmaceutical synthesis can be improved remains a central priority of biomedical research. The elucidation of novel reaction types that enable enantioselective organic transformations remains fundamental to this endeavor. The research proposed within this grant application is concerned with the discovery, improvement and application of versatile new catalysts and reaction pathways for asymmetric carbon-nitrogen and carbon-carbon bond formation. During the preceding funding period of GM 32000, the Principal Investigator and his coworkers have shown that a variety of non-metallocene complexes of the group 3 metals (particularly yttrium, scandium, lanthanum, lutetium and neodymium) are versatile and highly selective catalysts for the intramolecular hydroamination of carbon-carbon multiple bonds, intramolecular hydroamination / internal alkyne carbometallation cascades and PhSiHS alkene and diene hydrosilylations. Significantly, our second-generation chiral catalysts exhibit the highest enantioselectivities reported to date for asymmetric intramolecular alkene hydroamination. In addition, we have recently developed a neutral Zr(IV) catalyst that has superb activity for the hydroamination of alkynes and allenes. It is expected that the use of these new catalyst types, as well as structurally modified variants of them, will permit rapid access to important classes of heterocyclic intermediates for pharmacological research. This proposal outlines our immediate plans for the pursuit of this objective and details specific applications to the synthesis of selected bioactive molecules. [unreadable] [unreadable] [unreadable]